Synthesis of New Isoxazolidine Derivatives Utilizing the Functionality of N-Carbonylpyrazol-Linked Isoxazolidines

Using Ni(II) as the catalyst, electron-deficient 3,5-dimethylacryloylpyrazole olefin was reacted with C,N-diarylnitrones alone for 10 min to prepare novel five-member heterocyclic products, 4-3,5-dimethylacryloylpyrazole isoxazolidines with 100% regioselectivity and up to 99% yield. And then, taking these cycloadducts as substrates, six kinds of derivatization reactions, like ring-opening, nucleophilic substitution, addition-elimination and reduction, were studied. Experimental results showed that all kinds of transformations could obtain the target products at a high conversion rate under mild conditions, a finding which provided the basic methods for organic synthesis methodology research based on an isoxazolidine skeleton.


Introduction
Isoxazolidine compounds are a part of the azole family and contain O and N atoms in the 1,2-positions; these compounds serve as influential building blocks for bioactive molecules and natural products [1,2].Also, isoxazolidine compounds are often utilized as multipurpose intermediates in research subjects as diverse as organic synthesis, medicinal chemistry and material science [3][4][5].Among the existing methods, the 1,3-dipolar cycloaddition of nitrone with olefin is an important method used to gain structurally diverse isoxazolidines [6,7].The molecular structure of nitrones and alkenes plays a key role in the rate, selectivity and conversion of the cycloaddition reaction; therefore, selecting auxiliary groups with good inducing functions for nitrones and alkenes is of great significance.On the other hand, as can be seen from the structural characteristics of olefin, the leaving activity of the olefin auxiliary group is all-important in researching whether other active functional groups can be easily introduced into the isoxazolidine rings.
A previous work reported by our group showed that 3,5-dimethylpyrazolylcarbonyl olefin is an excellently reactive electron-deficient olefin in the 1,3-dipole cycloaddition reaction [8].However, (pyrazolylcarbonyl)isoxazolidine derivatizations are rarely systematically studied.In view of this, we attempted to modify isoxazolidine intermediates by employing 3,5-dimethylpyrazolylcarbonyl as an acylating reagent in the study of isoxazolidine derivatization.
Due to the outstanding performance of the isoxazolidine structural fragment in various fields, the construction of novel isoxazolidine derivants through simple and effective synthetic methods has long been a hot topic among organic synthetic chemists.In general, most of the works investigating isoxazolidines-involved derivatization reactions focus on the study of ring-opening reduction to form β-alkamine, and the rearrangement to form amino alcohols and preparation as lactams [9][10][11][12].Meanwhile, the 4-isoxazolidine derivatives with varying substituents exemplify an important way of increasing the application value of these compounds, since they retain the heterocyclic skeletons and also provide reaction sites in synthetic chemistry [13,14].Figure 1 shows the 4-substituted isoxazolidine derivatives in several drug molecules or natural products [15][16][17][18].
In this paper, novel 4-functionalized isoxazolidines attaching a 3,5-dimethylpyrazolylcarbonyl group with 100% regioselectivity and up to 99% yield were synthesized through a 1,3-dipolar cycloaddition process of C,N-diarylnitrones to 3,5-dimethylacryloylpyrazole alkene using a Ni (II) catalyst.Subsequently, we exploited six kinds of transformations, including ring-opening, nucleophilic substitution, and reduction, to construct a series of new 4-substituted isoxazolidine derivatives with moderate to excellent yields under mild conditions; the specific routes are shown in Figure 2.

Results and Discussion
In this paper, firstly, 4-(3,5-dimethylpyrazol-1-ylcarbonyl) isoxazolidines (1-6) were synthesized, and secondly, six kinds of isoxazolidine derivatives (7-40) were synthesized from these ingredients.The structures and yields of the isoxazolidines and their derivatives are shown in Figure 3.In this paper, novel 4-functionalized isoxazolidines attaching a 3,5-dimethylpyrazolylcarbonyl group with 100% regioselectivity and up to 99% yield were synthesized through a 1,3dipolar cycloaddition process of C,N-diarylnitrones to 3,5-dimethylacryloylpyrazole alkene using a Ni (II) catalyst.Subsequently, we exploited six kinds of transformations, including ring-opening, nucleophilic substitution, and reduction, to construct a series of new 4-substituted isoxazolidine derivatives with moderate to excellent yields under mild conditions; the specific routes are shown in Figure 2.
Molecules 2024, 29, 3454 2 of 12 derivatives with varying substituents exemplify an important way of increasing the application value of these compounds, since they retain the heterocyclic skeletons and also provide reaction sites in synthetic chemistry [13,14].Figure 1 shows the 4-substituted isoxazolidine derivatives in several drug molecules or natural products [15][16][17][18].In this paper, novel 4-functionalized isoxazolidines attaching a 3,5-dimethylpyrazolylcarbonyl group with 100% regioselectivity and up to 99% yield were synthesized through a 1,3-dipolar cycloaddition process of C,N-diarylnitrones to 3,5-dimethylacryloylpyrazole alkene using a Ni (II) catalyst.Subsequently, we exploited six kinds of transformations, including ring-opening, nucleophilic substitution, and reduction, to construct a series of new 4-substituted isoxazolidine derivatives with moderate to excellent yields under mild conditions; the specific routes are shown in Figure 2.

Study of the Reduction Reactions of (Pyrazolylcarbonyl)isoxazolidines
As depicted in Figure 4, the (pyrazolylcarbonyl)isoxazolidine-derived molecule had two easily reducible reactive sites (a and b), which created the possibility of the preparation of diverse isoxazolidine derivatives.Currently, the study of isoxazolidine derivatizations is mainly focused on the ring-opening hydrogenation reduction (in the site a) to acquire β-alkamine with the aid of suitable reducing agents.Compared to the isoxazolidine ring, due to the high reactivity of the pyrazolylcarbonyl, the carbonyl group in this structure is more prone to reduction reactions.Therefore, the methodology of choosing the appropriate reducing agent and selectively opening the isoxazolidine ring while retaining the pyrazole group to prepare new β-alkamines or retaining the isoxazolidine ring to prepare the 4position carbonyl group-reduced products is a challenging task.Some known samples have revealed ring-opening reduction catalysts like Raney-Ni [19], Zn/H + [20], Mo(CO) 6 [21] and Pd/C [22,23], which have catalyzed ring-opening reductions of isoxazolidine to generate β-alkamine.The experiment described, however, found that only the 3,5-dimethylpyrazolyl group was unaffected within the method of Pd/C catalyst hydrogenation.Given this, the effects of different groups of (pyrazolylcarbonyl)isoxazolidines on the reduction reaction were investigated by the use of a Pd/C catalyst.

Study of the Reduction Reactions of (Pyrazolylcarbonyl)isoxazolidines
As depicted in Figure 4, the (pyrazolylcarbonyl)isoxazolidine-derived molecule had two easily reducible reactive sites (a and b), which created the possibility of the preparation of diverse isoxazolidine derivatives.Currently, the study of isoxazolidine derivatizations is mainly focused on the ring-opening hydrogenation reduction (in the site a) to acquire β-alkamine with the aid of suitable reducing agents.Compared to the isoxazolidine ring, due to the high reactivity of the pyrazolylcarbonyl, the carbonyl group in this structure is more prone to reduction reactions.Therefore, the methodology of choosing the appropriate reducing agent and selectively opening the isoxazolidine ring while retaining the pyrazole group to prepare new β-alkamines or retaining the isoxazolidine ring to prepare the 4-position carbonyl group-reduced products is a challenging task.Some known samples have revealed ring-opening reduction catalysts like Raney-Ni [19], Zn/H + [20], Mo(CO)6 [21] and Pd/C [22,23], which have catalyzed ring-opening reductions of isoxazolidine to generate β-alkamine.The experiment described, however, found that only the 3,5-dimethylpyrazolyl group was unaffected within the method of Pd/C catalyst hydrogenation.Given this, the effects of different groups of (pyrazolylcarbonyl)isoxazolidines on the reduction reaction were investigated by the use of a Pd/C catalyst.As for the ring-opening hydrogenation reduction of (pyrazolylcarbonyl)isoxazolidines, Table 2 showed that the differences in the groups of (pyrazolylcarbonyl)isoxazolidines had a relatively large influence, causing significant differences in the reaction times and product yields.The yield of product 7 was 87% for 2 h when the benzene ring Ar 2 of the N-atom had no substituent (Entry 1).When the benzene ring of Ar 2 contained electrondonating substituents (-CH3 and -C2H5), the yields of 8 and 9 were distinctly increased to 95%, although the reaction time was shortened to 1 h (Entries 2-3).When the benzene ring of Ar 2 contained electron-withdrawing groups (-Cl and -CN) and the Ar 1 substituent was the 9-anthryl group, products 10, 11 and 12 had, respectively, yields of 70, 84 and 60%, and respective reaction times of 8, 3 and 8 h (Entries 4-6).It is known that 4-hydroxymethylated isoxazolidine derivants have some uses in medicinal chemistry and other subjects [24,25].Here, the use of sodium borohydride (NaBH4) to induce the reduction reaction of As for the ring-opening hydrogenation reduction of (pyrazolylcarbonyl)isoxazolidines, Table 2 showed that the differences in the groups of (pyrazolylcarbonyl)isoxazolidines had a relatively large influence, causing significant differences in the reaction times and product yields.The yield of product 7 was 87% for 2 h when the benzene ring Ar 2 of the N-atom had no substituent (Entry 1).When the benzene ring of Ar 2 contained electron-donating substituents (-CH 3 and -C 2 H 5 ), the yields of 8 and 9 were distinctly increased to 95%, although the reaction time was shortened to 1 h (Entries 2-3).When the benzene ring of Ar 2 contained electron-withdrawing groups (-Cl and -CN) and the Ar 1 substituent was the 9-anthryl group, products 10, 11 and 12 had, respectively, yields of 70, 84 and 60%, and respective reaction times of 8, 3 and 8 h (Entries 4-6).It is known that 4-hydroxymethylated isoxazolidine derivants have some uses in medicinal chemistry and other subjects [24,25].Here, the use of sodium borohydride (NaBH 4 ) to induce the reduction reaction of isoxazolidines was studied.When the molar ratio of reactant to NaBH 4 was 1:4, a yield of 13 achieved a maximum value of 92% for 5 h (Entries 7).The effects of substituents of (pyrazolylcarbonyl)isoxazolidines on the reaction were also studied, and the results showed that differences in the substituents had little effect on the reactions under the same conditions (Entries 8-12).

Study of the Nucleophilic Reactions of (Pyrazolylcarbonyl)isoxazolidines
From the perspective of some works in the literature and potential applications [26][27][28], the introduction of four functional groups (-C(CH3)2OH, -COCH3, -CONHNH2 and -COOC2H5) into the 4-position of the isoxazolidine ring was very important.Therefore, the involvement of the 3,5-dimethylpyrazolylcarbonyl group in the derivatization reactions broadened the synthetic utility of the isoxazolidines.
Initially, the product was generated in the tertiary alcohol stage by controlling the input amount of the CH3MgBr.There was hardly any reaction when the amount of CH3MgBr was lower than 1 equivalent at 0 °C (Entries 1-2).When the amount of CH3MgBr

Study of the Nucleophilic Reactions of (Pyrazolylcarbonyl)isoxazolidines
From the perspective of some works in the literature and potential applications [26][27][28], the introduction of four functional groups (-C(CH 3 ) 2 OH, -COCH 3 , -CONHNH 2 and -COOC 2 H 5 ) into the 4-position of the isoxazolidine ring was very important.Therefore, the involvement of the 3,5-dimethylpyrazolylcarbonyl group in the derivatization reactions broadened the synthetic utility of the isoxazolidines.

Study of the Nucleophilic Substitution Reactions with Organometallic Reagents
The involvement of (pyrazolylcarbonyl)isoxazolidine in a nucleophilic substitution reaction with Grignard reagent CH 3 MgBr constituted an efficient method to obtain 2-(2-(aryl)-3-arylisoxazolidin-4-yl)propan-2-ol (19)(20)(21)(22)(23)(24) in 70-75% yields at 0 • C for 2 h under argon.To retain a methyl ketone fragment, we tried to lower the amount of CH 3 MgBr and the reaction temperature.However, the stronger leaving property of the 3,5-dimethylpyrazolylcarbonyl group and the stronger reactivity of CH 3 MgBr led to the methyl ketones produced being eventually converted into tertiary alcohols.To address this, CH 3 MgBr was replaced with the less reactive (CH 3 ) 2 CuLi, and 4-acetyl-2,3-diarylisoxazolidines (25-28) with methyl ketone fragments in 65-70% yields were obtained under the same conditions (Table 3).fluoroethylene stir-bar surface exposed a small amount of iron dust in the original reaction system.Simultaneously, we consulted some literature on nucleophilic substitution reactions involving organometallic reagents and found that iron catalysts could catalyze this reaction.Subsequently, we tried using iron powder as catalyst, and the experimental results showed that the reaction could proceed smoothly [29].Hence, when the molar ratio of (pyrazolylcarbonyl)isoxazolidine and (CH3)2CuLi was 1:3, acetylation products were obtained with a trace amount of Fe powder catalysis at 0 °C under argon (Entries 18-21).Initially, the product was generated in the tertiary alcohol stage by controlling the input amount of the CH 3 MgBr.There was hardly any reaction when the amount of CH 3 MgBr was lower than 1 equivalent at 0 • C (Entries 1-2).When the amount of CH 3 MgBr increased to 1, 5 and 10 equivalents, the yields of product 19 with a tertiary alcohol structure reached 7%, 30% and 73% for 2 h, respectively (Entries 3-7).Additionally, the target had an identical yield (73%) for 30 min when using 11-equivalent amounts of CH 3 MgBr (Entry 8).The ingredients disappeared and only a small amount of product was synthesized across a duration of 30 min when the reaction temperature was raised to room temperature (Entry 9), possibly because the hyperalkalinity of CH 3 MgBr caused the decomposition of both the ingredients and the product.Further, 19 had respective yields of only 65% and 52% when the amount of CH 3 MgBr was 11 equivalents and the reaction temperature was further reduced to −10 • C and −20 • C for 3 h (Entries 10-11).Meanwhile, experiment's results showed that different groups of 4-(pyrazolylcarbonyl)isoxazolidines had little effect on the reaction under the 10-equivalent amounts of CH 3 MgBr for 2 h at 0 • C (Entries 12-16).
4-Acetyl-2,3-diarylisoxazolidines (25)(26)(27)(28) in 68-70% yields were readily prepared when using 3-equivalent amounts of the less reactive (CH 3 ) 2 CuLi at 0 • C. Unexpectedly, the reaction could not be reproduced when the experiment was repeated later (Entry 17).We carefully observed and studied the experimental results and found that the polytetrafluoroethylene stir-bar surface exposed a small amount of iron dust in the original reaction system.Simultaneously, we consulted some literature on nucleophilic substitution reactions involving organometallic reagents and found that iron catalysts could catalyze this reaction.Subsequently, we tried using iron powder as catalyst, and the experimental results showed that the reaction could proceed smoothly [29].Hence, when the molar ratio of (pyrazolylcarbonyl)isoxazolidine and (CH 3 ) 2 CuLi was 1:3, acetylation products were obtained with a trace amount of Fe powder catalysis at 0 • C under argon (Entries 18-21).

Study of the Hydrazinolysis and Alcoholysis Reactions of (Pyrazolylcarbonyl)isoxazolidines
To explore the nucleophilicity of (pyrazolylcarbonyl)isoxazolidines toward 80w% hydrazine hydrate, hydrazinolysis reactions were performed under mild conditions (Table 4).When there was no substituent in the benzene ring of (pyrazolylcarbonyl)isoxazolidines, the yield of 29 reached 70% at 0 • C for 1 h (Entry 1).The yield of product was reduced to 45% when the reaction temperature was raised to room temperature (Entry 2), likely due to the strong alkalinity of 80w% hydrazine hydrate, which led to partial hydrolysis of the (pyrazolylcarbonyl)isoxazolidine [30].The yield of product was increased to 92% when reaction time was extended to 3 h at 0 • C (Entries 3-4), and the yield of product slightly roset (93% yield) when the reaction time was prolonged to 4 h (Entry 5).When the benzene ring on the N-atom contained electron-donating groups (-CH 3 , -C 2 H 5 ), the yields of compounds 30 and 31 reached 93% and 95%, respectively (Entries 6-7).When it contained electron-withdrawing groups (-Cl, -CN), compounds 32 and 33 had respective yields of 92% and 91% (Entries 8-9).And when the benzene ring on Ar 1 was replaced with a larger volume of 9-anthryl, the yield of 34 reached 90% for 3 h (Entry 10).To explore the nucleophilicity of (pyrazolylcarbonyl)isoxazolidines toward 80w% hydrazine hydrate, hydrazinolysis reactions were performed under mild conditions (Table 4).When there was no substituent in the benzene ring of (pyrazolylcarbonyl)isoxazolidines, the yield of 29 reached 70% at 0 °C for 1 h (Entry 1).The yield of product was reduced to 45% when the reaction temperature was raised to room temperature (Entry 2), likely due to the strong alkalinity of 80w% hydrazine hydrate, which led to partial hydrolysis of the (pyrazolylcarbonyl)isoxazolidine [30].The yield of product was increased to 92% when reaction time was extended to 3 h at 0 °C (Entries 3-4), and the yield of product slightly roset (93% yield) when the reaction time was prolonged to 4 h (Entry 5).When the benzene ring on the N-atom contained electron-donating groups (-CH3, -C2H5), the yields of compounds 30 and 31 reached 93% and 95%, respectively (Entries 6-7).When it contained electron-withdrawing groups (-Cl, -CN), compounds 32 and 33 had respective yields of 92% and 91% (Entries 8-9).And when the benzene ring on Ar 1 was replaced with a larger volume of 9-anthryl, the yield of 34 reached 90% for 3 h (Entry 10).Next, to explore the nucleophilicity of (pyrazolylcarbonyl)isoxazolidines toward nucleophiles, the effects of varying nucleophile dosages, reaction temperatures, reaction times and varying groups of isoxazolidines within the alcoholysis reaction were tested (Table 5).Using methods described in the literature [23,31], no products were generated, according to TLC analysis, when using a 0.8 equivalent of sodium methoxide (CH3ONa) at room temperature for 30 min (Entry 1), probably because the strong reactivity of CH3ONa led to the loss of ingredients thorough decomposition.Products 35′ had respective yields of 60% and 73% when using 0.8 equivalent and 1.1 equivalents of CH3ONa at 0 °C for 5 min (Entries 2-3).However, the utilization of 1.1 equivalents of sodium ethoxide (EtONa) further enhanced the yield of 35 (93% yield) at 0 °C for 5 min (Entry 4).With the continuous extension of the reaction time, the quantity of the products would gradually become less until the product almost completely disappeared after 25 min (Entries 5-8).The yield of product was significantly reduced when using less than 1  Next, to explore the nucleophilicity of (pyrazolylcarbonyl)isoxazolidines toward nucleophiles, the effects of varying nucleophile dosages, reaction temperatures, reaction times and varying groups of isoxazolidines within the alcoholysis reaction were tested (Table 5).Using methods described in the literature [23,31], no products were generated, according to TLC analysis, when using a 0.8 equivalent of sodium methoxide (CH 3 ONa) at room temperature for 30 min (Entry 1), probably because the strong reactivity of CH 3 ONa led to the loss of ingredients thorough decomposition.Products 35 ′ had respective yields of 60% and 73% when using 0.8 equivalent and 1.1 equivalents of CH 3 ONa at 0 • C for 5 min (Entries 2-3).However, the utilization of 1.1 equivalents of sodium ethoxide (Et-ONa) further enhanced the yield of 35 (93% yield) at 0 • C for 5 min (Entry 4).With the continuous extension of the reaction time, the quantity of the products would gradually become less until the product almost completely disappeared after 25 min (Entries 5-8).The yield of product was significantly reduced when using less than 1 equivalent of EtONa (Entries 9-10).Consequently, when the molar ratio of (pyrazolylcarbonyl)isoxazolidine with EtONa was 1:1.1, ethyl 2,3-diarylisoxazolidin-4-ylcarboxylate (35-40) with 92-94% yields was gained at 0 • C for 5 min under argon (Entries 4 and 11-15).

Instrumentation and Materials
IR spectra were recorded by a Thermo Nicolet 370 Fourier transform infrared (FTIR) spectrometer, with the samples in KBr pellets.The 1 H and 13 C NMR spectra were obtained using a Bruker 300 NMR spectrometer (300 and 75 MHz, respectively) in CDCl3.Abbreviations for data cited are as follows: s, singlet; d, doublet; t, triplet; dd, doublet of doublets; m, multiplet.The residual solvent signals were served as references and the chemical shifts converted to the TMS scale (CDCl3: δH = 7.26 ppm, δC = 77.16ppm).High-resolution mass spectra were obtained on a Waters G2-XS QTof mass spectrometer.Melting points were determined with a Tektronix X-6 micro-melting-point apparatus and are uncorrected.
All chemicals and reagents were purchased from sellers and employed as received.

Synthesis Methods
The starting materials, specifically, the alkene and nitrones, were obtained according to a previously published method [32].

Instrumentation and Materials
IR spectra were recorded by a Thermo Nicolet 370 Fourier transform infrared (FTIR) spectrometer, with the samples in KBr pellets.The 1 H and 13 C NMR spectra were obtained using a Bruker 300 NMR spectrometer (300 and 75 MHz, respectively) in CDCl 3 .Abbreviations for data cited are as follows: s, singlet; d, doublet; t, triplet; dd, doublet of doublets; m, multiplet.The residual solvent signals were served as references and the chemical shifts converted to the TMS scale (CDCl 3 : δ H = 7.26 ppm, δ C = 77.16ppm).High-resolution mass spectra were obtained on a Waters G2-XS QTof mass spectrometer.Melting points were determined with a Tektronix X-6 micro-melting-point apparatus and are uncorrected.
All chemicals and reagents were purchased from sellers and employed as received.

Synthesis Methods
The starting materials, specifically, the alkene and nitrones, were obtained according to a previously published method [32].
Corresponding data and spectra are given in the Supplementary Materials.
3.2.3.Synthesis of 4-Hydroxymethyl-2,3-diphenylisoxazolidine (13-18) Compounds 1 or 2-6 (50 mg, 0.144 mmol) and NaBH 4 (21.79 mg, 0.576 mmol) were added to THF (4 mL) at 0 • C under a nitrogen atmosphere.The mixture was gradually returned to room temperature and continuously stirred for 5 h, and the reaction was monitored by TLC (R f = 0.33 (petroleum ether/ethyl acetate = 2/1)).The reaction mixture was quenched with a small amount of water, and then washed with saturated salt water and extracted with ethyl acetate, and the organic phase was evaporated in a vacuum.The crude product was purified by preparative TLC (eluent: PE/EA = 3/1) to obtain products 13-18.
Corresponding data and spectra are given in the Supplementary Materials.Compounds 1 or 2-6 (50 mg, 0.144 mmol) were dissolved in THF (4 mL), and next, a 3.0 M CH 3 MgBr solution in Et 2 O (480 µL, 1.44 mmol) was added dropwise at 0 • C under a nitrogen atmosphere.The mixture was gradually returned to room temperature and continuously stirred for 2 h, and the reaction was monitored by TLC (R f = 0.3 (PE/EA = 5/1)).The reaction mixture was quenched with a small amount of water, and then washed with saturated salt water and extracted with ethyl acetate, and the organic phase was evaporated in a vacuum.The crude product was purified by preparative TLC (eluent: PE/EA = 4/1) to obtain products 19-24.Corresponding data and spectra are given in the Supplementary Materials.3.2.5.Synthesis of 4-Acetyl-2,3-diarylisoxazolidines (25)(26)(27)(28) Compounds 1 or 2-6 (50 mg, 0.144 mmol) and Fe powder (25 mg, 0.447 mmol) were dissolved in CH 2 Cl 2 (4 mL), and next, a 0.5 M (CH 3 ) 2 CuLi solution in Et 2 O (864 µL, 0.432 mmol) was added dropwise at 0 • C under a nitrogen atmosphere.The mixture was gradually returned to room temperature and continuously stirred for 1 h, and the reaction was monitored by TLC (R f = 0.6 (PE/EA = 5/1)).The reaction mixture was quenched with a small amount of water, and then washed with saturated salt water and extracted with ethyl acetate, and the organic phase was evaporated in a vacuum.The crude product was purified by preparative TLC (eluent: PE/EA = 10/1) to gain products 25-28.Corresponding data and spectra are given in the Supplementary Materials.

Figure 2 .
Figure 2. The synthesis routes of isoxazolidines and their further derivatization reactions.

Figure 2 .
Figure 2. The synthesis routes of isoxazolidines and their further derivatization reactions.

Figure 2 .
Figure 2. The synthesis routes of isoxazolidines and their further derivatization reactions.

Figure 3 .
Figure 3.The structures and yields of isoxazolidines and their derivatives.
a Isolated yields.

Table 2 .
Effects of different groups of (pyrazolylcarbonyl)isoxazolidines on the Pd/C reduction reaction.

Table 2 .
Effects of different groups of (pyrazolylcarbonyl)isoxazolidines on the Pd/C reduction reaction.
a Isolated yields.

Table 3 .
Effect of different reaction factors on a metallic organics nucleophilic substitution reaction.

Table 3 .
Effect of different reaction factors on a metallic organics nucleophilic substitution reaction.
a Isolated yields.

Table 5 .
Effect of different reaction factors on the EtONa alcoholysis reaction.
a Isolated yields.